EP1363603A1 - Procede pour rendre hydrosoluble un antiseptique peu soluble dans l'eau - Google Patents
Procede pour rendre hydrosoluble un antiseptique peu soluble dans l'eauInfo
- Publication number
- EP1363603A1 EP1363603A1 EP02706888A EP02706888A EP1363603A1 EP 1363603 A1 EP1363603 A1 EP 1363603A1 EP 02706888 A EP02706888 A EP 02706888A EP 02706888 A EP02706888 A EP 02706888A EP 1363603 A1 EP1363603 A1 EP 1363603A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- water
- antiseptic
- granules
- mannitol
- soluble
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
Definitions
- the invention relates to a process for the preparation of water-soluble granules containing at least one antiseptic naturally poorly or not soluble in water, as well as to the uses of this process, and in particular for the preparation of pharmaceutical compositions in dry form and allowing solutions for mouthwashes to be produced immediately.
- the solutions for mouthwashes commercially available to date are hydro-ethanolic solutions, which are packaged in bottles in glass or plastic, with a capacity ranging from 125 to 500 ml, and which are impractical to use when one has to move, given their size and the risk of breakage and / or soiling if the bottle is not closed properly. This most often results in poor adherence to treatment by patients who avoid traveling with their bottle of mouthwash solutions.
- compositions in dry form preferably packaged in unit doses, easily transportable, and suitable for dom er, after dispersing in a volume of water. suitable, solutions for mouthwashes.
- Effervescent tablets have long been known for allowing the extemporaneous preparation of mouthwash solutions. Such tablets are, for example, described in U.S. Patents 3,772,431, 3,888,976 and 4,919,918. In all cases, these are general public products, more intended to allow cleaning of the oral cavity and teeth, by an effervescent or even foaming effect, than disinfection. Therefore, in these Patents, the presence of an antiseptic such as cetyldimethyl benzylammonium chloride or chlorhexidine, is only considered very incidentally.
- an antiseptic such as cetyldimethyl benzylammonium chloride or chlorhexidine
- patent application FR-A-2 649 611 proposes a process for the preparation of a therapeutic composition based on acetylsalicylic acid consisting in dissolving this active principle in a solvent and then impregnating the solution thus formed with a carbohydrate food support. then causing the solvent to evaporate to lead to the formation of microparticles or microcrystals of the active principle, the development of the crystals being limited by the matrix of the support.
- patent application FR-A-2 613 223 provides a process for the preparation of a solid dosage form in the form of water-soluble grains containing Ginkgo biloba. According to this process, this active principle and solubilized in a solvent in the presence of a surfactant, then this solution is then mixed with a water-soluble support which is then subjected to granulation.
- the water-soluble support can equally be chosen from sucrose, lactose, mannitol and maltodextrins.
- the inventors have therefore set themselves the goal of providing a process which makes it possible to make an antiseptic naturally sparingly or not soluble in water hydrosoluble, so as to be able to prepare pharmaceutical compositions in dry form which, although containing one or more poorly or not water-soluble antiseptics, are capable of forming homogeneous and stable solutions (without any phase shift phenomenon) after dispersion in water.
- the Inventors have, moreover, set themselves the goal of providing a process which, while having these advantages, is simple to implement and does not require any other apparatus than that with which the pharmaceutical laboratories are conventionally equipped.
- the invention therefore relates to a process for the preparation of water-soluble granules containing at least one antiseptic, comprising: a) a step of wet granulation or of impregnation of a pharmaceutically acceptable water-soluble support in the form of granules by means a solvent containing at least one active principle, and b) a step of drying the granules, characterized in that the water-soluble support in the form of granules is mannitol and that the active principle is an antiseptic.
- the inventors have not yet identified the nature of the bond which is established between the antiseptic active principle and mannitol during granulation. On the other hand, the existence of this bond could clearly be demonstrated by tests showing that, if one subjects a solution obtained by dispersion of the granules in water, to filtrations and extractions, one finds constantly the antiseptic active ingredient in the fraction where mannitol is found, without any trace of antiseptic not linked to mannitol being detected.
- the solvent used for the granulation or the impregnation is water, an alcohol or a water-alcohol mixture.
- the inventors have, in fact, found that it is not necessary for the antiseptic to bind properly to mannitol for it to be dissolved in the solvent, so that the latter can be water as well which the antiseptic is in suspension than an alcohol or a hydro-alcoholic mixture in which it is in solution.
- the solvent is an alcohol or a water-alcohol mixture
- ethanol is preferably used.
- other alcohols such as isopropanol are also capable of being used for the implementation of the process according to the invention.
- the antiseptic is chosen from quaternary ammonium, hexetidine, bisbiguanides, chlorhexidine and its salts such as hydrochloride or acetate of chlorhexidine, chlorobutanol hemihydrate, eugenol, eucalyptol, tyrothricin and essential oils like peppermint essential oil.
- this antiseptic can be combined with one or more other active principles, antiseptic or not, depending on the therapeutic effect sought, which can either also have a low or zero solubility in water, or be, them, perfectly soluble in water, as is the case in particular with chlorhexidine digluconate, choline salicylate and certain quaternary ammoniums known to have good water solubility (cetyl pyridinium chloride for example) which is commonly associated with chlorobutanol hemihydrate and hexetidine.
- active principles antiseptic or not, depending on the therapeutic effect sought, which can either also have a low or zero solubility in water, or be, them, perfectly soluble in water, as is the case in particular with chlorhexidine digluconate, choline salicylate and certain quaternary ammoniums known to have good water solubility (cetyl pyridinium chloride for example) which is commonly associated with chlorobutanol hemihydrate and hexetidine.
- the active ingredients that one wishes to combine have very different solubilities, it is preferable to dissolve them in two different solvents (for example, an alcohol for the least soluble active ingredient, water or a water-alcohol mixture for the most soluble active principle) and granulating the mannitol by wetting the latter first with the solvent containing the least soluble active principle, then with the solvent containing the most soluble active principle.
- solvents for example, an alcohol for the least soluble active ingredient, water or a water-alcohol mixture for the most soluble active principle
- the solvent used for the granulation or impregnation of mannitol can also comprise one or more excipients such as a dye (amaranth, cochineal red, patent blue V, etc.) chosen for its compatibility with the antiseptic used and the optional active ingredient (s) intended to impart a pleasant color to the solution resulting from the dispersion of the granules in water, or any other excipient which it is desired to combine with the antiseptic and which also presents , low or no water solubility.
- excipients such as a dye (amaranth, cochineal red, patent blue V, etc.) chosen for its compatibility with the antiseptic used and the optional active ingredient (s) intended to impart a pleasant color to the solution resulting from the dispersion of the granules in water, or any other excipient which it is desired to combine with the antiseptic and which also presents , low or no water solubility.
- the granulation or impregnation is carried out with an amount of solvent corresponding to 10 to 80% and, preferably, to 15 to 75% by weight of the weight of the mannitol, while this solvent has a content by weight of antiseptic of between 10 and 80% and, preferably, between 15 and 70%.
- the latter advantageously have a weight ratio between the mannitol and the antiseptic of between 0.5 and 50 and, preferably, between 1 and 30.
- the granulation of the mannitol and the drying of the granules are preferably carried out in a fluidized air bed at a temperature which can vary between 20 and 60 ° C. depending on the degree of heat sensitivity of the at least one antiseptics and any additional active ingredient (s) used.
- a temperature which can vary between 20 and 60 ° C. depending on the degree of heat sensitivity of the at least one antiseptics and any additional active ingredient (s) used.
- this comprises, after the granules have dried, a calibration operation of these granules, for example by sieving on a grid, this calibration preferably being carried out by so as to eliminate all the granules having a size greater than 5 mm.
- the process which has just been described has numerous advantages. In fact, by making it possible to make water-soluble antiseptics which naturally are not or only slightly, it offers the possibility of producing, from antiseptics with low or no water solubility, compositions in dry form and suitable to form homogeneous and stable solutions after dispersion in water. Furthermore, this process is simple to implement and uses only raw materials (mannitol, water, alcohol) readily available and at a cost compatible with exploitation on an industrial scale. Finally, it does not require any specific equipment and can be implemented by means of the equipment with which pharmaceutical laboratories are conventionally equipped, wet granulation and impregnation being in fact commonly used for the manufacture of medicaments proposed in capsules. and in tablets.
- the invention also relates to the use of a process as defined above for the preparation of a pharmaceutical composition in dry form and capable of giving extemporaneously a solution for mouthwashes, after dispersion in the water.
- the invention therefore also relates to a pharmaceutical composition which is in a dry form and which makes it possible to produce an extemporaneous solution for a mouthwash, by dispersion in water, which is characterized in that it comprises granules formed from mannitol linked to at least one antiseptic.
- the antiseptic is chosen from quaternary ammoniums, hexetidine, bisbiguanides, chlorhexidine and its salts such as chlorhexidine hydrochloride or acetate, chlorobutanol hemihydrate, eugenol, l eucalyptol, tyrothricin and essential oils like peppermint.
- the antiseptic is chosen from hexetidine and chlorobutanol hemihydrate, optionally in combination with chlorhexidine digluconate.
- the composition can consist solely of granules as obtained by the process described above.
- mannitol is itself a sweetener and contributes to giving the composition both a sweetness and a freshness in the mouth
- one or more sweeteners such as sodium cyclamate , sodium saccharinate, aspartame or ammonium glycerinate, and / or one or more flavors (mint, anise, lemon, raspberry, ...) to make it even more pleasant, both in terms of taste and its fragrance, especially in the case where the antiseptic used has not very advantageous organoleptic qualities.
- the composition may be in the form of a powder resulting from the mixture of the granules with the excipient (s), or in the form of tablets.
- the composition also comprises one or more excipients chosen from those conventionally used for the compression of powders or granules such as flow agents, filling agents and lubricating agents.
- each unit dose is packaged in an airtight and water-tight packaging, such as for example a sachet formed of an aluminum foil lined with a polyethylene film, and the dimensions of which are chosen so as to be able to contain, once opened, a volume sufficient water to perform a mouthwash, which avoids the use of a glass that is not always at hand, especially when moving.
- an airtight and water-tight packaging such as for example a sachet formed of an aluminum foil lined with a polyethylene film, and the dimensions of which are chosen so as to be able to contain, once opened, a volume sufficient water to perform a mouthwash, which avoids the use of a glass that is not always at hand, especially when moving.
- the composition according to the invention has many advantages. Indeed, it disperses easily in water to form a clear, homogeneous, stable solution with a very pleasant taste, even when it contains an antiseptic with organoleptic properties which are not very advantageous. Being in a dry form, it eliminates the risks of degradation of antiseptics tending to be unstable in solution as is mainly the case of chlorhexidine whose stability depends closely on the alcoholic degree and. pH. Presented in unit dosages, it guarantees the use of an effective dose of antiseptic during each mouthwash. Finally, due to its presentation and its ease of use, it offers the possibility of carrying out a mouthwash in any circumstance without having to move around with a bottle liable to break or open unexpectedly.
- the invention also relates to a solution for mouthwashes, characterized in that it is obtained by dispersing in water a pharmaceutical composition as defined above.
- EXAMPLE 1 Composition comprising hexetidine as active ingredient
- 100,000 sachets are produced, each containing 540.54 mg of a composition in the form of granules and having the following formulation:
- EXAMPLE 2 Composition comprising chlorhexidine digluconate and chlorobutanol hemihydrate 100,000 sachets are prepared, each containing 590.171 mg of a composition in the form of granules and having the following formulation:
- compositions 1 and 2 - The ability of the compositions prepared in accordance with Examples 1 and 2 - and hereinafter called compositions 1 and 2 - to form homogeneous and stable solutions after dispersion in water was demonstrated, on the one hand, visually to verify the absence of phase shift phenomenon, and, on the other hand, by analyzes aiming to measure the diameter of the particles present in samples obtained by dispersion of these compositions in water.
- the samples were prepared by dispersing the content of one sachet - i.e. 540.54 mg of composition for composition 1 and 590.171 mg of composition for composition 2 - in 20 ml of water, and the analyzes were carried out using a laser diffraction particle size analyzer (He-Ne red laser of 2 mW minimum, 18 mm in diameter and 633 nm in wavelength) MASTERSIZER BANC LONG (Company MALVERN INSTRUMENTS SA) and an MSI sampler from the same Company.
- a laser diffraction particle size analyzer He-Ne red laser of 2 mW minimum, 18 mm in diameter and 633 nm in wavelength
- MASTERSIZER BANC LONG Company MALVERN INSTRUMENTS SA
- MSI sampler from the same Company.
- Figures 1 to 3 illustrate, both in the form of histograms and curves, the particle size distributions obtained respectively for the samples prepared from composition 1 and composition 2, and a hydro-ethanolic solution for reference mouthwash: the Hextril ®, which hexetidine for active ingredient as Composition 1.
- the abscissa axis represents the diameter, expressed in ⁇ m, of the particles present in the solutions
- the left ordinate axis represents the percentage of each population of particles - a population corresponding to a hatched rectangle -
- the ordinate axis on the right represents the cumulative percentages of the particle populations.
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Cosmetics (AREA)
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK02706888T DK1363603T3 (da) | 2001-03-01 | 2002-02-22 | Fremgangsmåde til at göre et tungt vandoplöseligt antiseptisk middel vandoplöseligt |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0102794A FR2821552B1 (fr) | 2001-03-01 | 2001-03-01 | Procede pour rendre hydrosoluble un principe actif naturellement peu ou pas soluble dans l'eau et ses utilisations |
FR0102794 | 2001-03-01 | ||
PCT/FR2002/000663 WO2002069931A1 (fr) | 2001-03-01 | 2002-02-22 | Procede pour rendre hydrosoluble un antiseptique naturellement peu ou pas soluble dans l'eau et ses utilisations |
Publications (2)
Publication Number | Publication Date |
---|---|
EP1363603A1 true EP1363603A1 (fr) | 2003-11-26 |
EP1363603B1 EP1363603B1 (fr) | 2005-06-01 |
Family
ID=8860604
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP02706888A Expired - Lifetime EP1363603B1 (fr) | 2001-03-01 | 2002-02-22 | Procede pour rendre hydrosoluble un antiseptique peu soluble dans l'eau |
Country Status (9)
Country | Link |
---|---|
US (1) | US20040137053A1 (fr) |
EP (1) | EP1363603B1 (fr) |
AT (1) | ATE296620T1 (fr) |
CA (1) | CA2445305A1 (fr) |
DE (1) | DE60204430T2 (fr) |
ES (1) | ES2243694T3 (fr) |
FR (1) | FR2821552B1 (fr) |
PT (1) | PT1363603E (fr) |
WO (1) | WO2002069931A1 (fr) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2919802B1 (fr) * | 2007-08-06 | 2011-05-06 | Cll Pharma | Procede de solubilisation d'huiles essentielles dans l'eau |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3772431A (en) * | 1972-09-21 | 1973-11-13 | W Mlkvy | Effervescent mouthwash tablet |
FR2613223B1 (fr) * | 1987-04-03 | 1991-09-13 | Biogalenique Laboratoires | Forme galenique se presentant sous la forme de grains hydrosolubles, en particulier a base d'un extrait sec de ginkgo biloba, et son procede de preparation |
FR2649611A1 (fr) * | 1989-07-13 | 1991-01-18 | Philippe Perovitch | Procede de preparation galenique d'une composition therapeutique notamment a base d'aspirine |
WO2000023040A1 (fr) * | 1998-10-16 | 2000-04-27 | Fuisz Technologies Ltd. | Composition desodorisante seche pour administration buccale |
-
2001
- 2001-03-01 FR FR0102794A patent/FR2821552B1/fr not_active Expired - Fee Related
-
2002
- 2002-02-22 US US10/469,603 patent/US20040137053A1/en not_active Abandoned
- 2002-02-22 DE DE60204430T patent/DE60204430T2/de not_active Expired - Fee Related
- 2002-02-22 EP EP02706888A patent/EP1363603B1/fr not_active Expired - Lifetime
- 2002-02-22 ES ES02706888T patent/ES2243694T3/es not_active Expired - Lifetime
- 2002-02-22 PT PT02706888T patent/PT1363603E/pt unknown
- 2002-02-22 WO PCT/FR2002/000663 patent/WO2002069931A1/fr not_active Application Discontinuation
- 2002-02-22 AT AT02706888T patent/ATE296620T1/de not_active IP Right Cessation
- 2002-02-22 CA CA002445305A patent/CA2445305A1/fr not_active Abandoned
Non-Patent Citations (1)
Title |
---|
See references of WO02069931A1 * |
Also Published As
Publication number | Publication date |
---|---|
ATE296620T1 (de) | 2005-06-15 |
FR2821552A1 (fr) | 2002-09-06 |
ES2243694T3 (es) | 2005-12-01 |
DE60204430D1 (de) | 2005-07-07 |
EP1363603B1 (fr) | 2005-06-01 |
CA2445305A1 (fr) | 2002-09-12 |
WO2002069931A1 (fr) | 2002-09-12 |
DE60204430T2 (de) | 2006-03-16 |
PT1363603E (pt) | 2005-10-31 |
FR2821552B1 (fr) | 2004-07-09 |
US20040137053A1 (en) | 2004-07-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
FR2919802A1 (fr) | Procede de solubilisation d'huiles essentielles dans l'eau | |
TWI310315B (en) | Taste masking of essential oils using a hydrocolloid | |
CA2579673C (fr) | Composition pharmaceutique comprenant une dispersion solide a matrice polymere comprenant une phase continue de polydextrose et une phase continue d'un polymere autre que du polydextrose | |
CA2219475C (fr) | Composition pharmaceutique de fenofibrate presentant une biodisponibilite elevee et son procede de preparation | |
CA2471903A1 (fr) | Poudre micronisee pharmaceutique ou nutraceutique a liberation immediate. | |
FR2832632A1 (fr) | Capsule a solubilisation et liberation du contenu rapides | |
CA2643330A1 (fr) | Comprimes d'oxycodone resistant a l'ecrasement destines a eviter le mesusage involontaire et le detournement illicite | |
FR2601876A1 (fr) | Composition pharmaceutique hydrosoluble contenant de la n-acetyl-cysteine et de l'acide citrique | |
EP2131823B1 (fr) | Film monocouche a desintegration rapide pour l'administration buccale de substances actives | |
CA2697893A1 (fr) | Composition solide, orodispersible et/ou dispersible, sans excipient a effet notoire et son procede de preparation | |
EP2985018B1 (fr) | Composition anti-décoloration | |
EP1363603B1 (fr) | Procede pour rendre hydrosoluble un antiseptique peu soluble dans l'eau | |
EP3007675A1 (fr) | Microparticules avec des cyclodextrines à double niveau d'encapsulation | |
CH707354B1 (fr) | Composition pharmaceutique sous la forme d'une suspension orale comprenant une fraction flavonoïque à base de diosmine et de la gomme xanthane. | |
EP0751759B1 (fr) | Lotion capillaire a base de minoxidil | |
CA2747860C (fr) | Composition cosmetique comprenant un hydrolysat de gomme de caroube | |
EP3212164B1 (fr) | Granules de principe actif a double masquage de gout, leur procede de preparation et comprimes orodispersibles les contenant | |
EP4045016B1 (fr) | Comprimé à libération prolongée de la molsidomine | |
FR2791888A1 (fr) | Suspension pharmaceutique buvable | |
FR2741532A1 (fr) | Nouvelles compositions pharmaceutiques a action antimigraineuse et leur mode de preparation | |
FR3122086A1 (fr) | Comprimé à sucer à base de PVPI dépourvu d’excipients cellulosiques. | |
EP1935412A2 (fr) | Composition pharmaceutique contenant de la 5-chloro-1-[1-[3-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)propyl]pipéridin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one et son procede de preparation | |
EP0666075B1 (fr) | Composition cosmétique ou dermatologique contenant une dispersion aqueuse de particules solides d'un homopolymère-filtre U.V. | |
FR2750859A1 (fr) | Composition pharmaceutique destinee a une administration par voie buccale avec absorption d'au moins un principe actif a travers les muqueuses de la bouche | |
CH712181A2 (fr) | Granulés non effervescents contenant de la N-acétylcystéine. |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20030916 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR |
|
AX | Request for extension of the european patent |
Extension state: AL LT LV MK RO SI |
|
GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
RAP3 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: CLL PHARMA |
|
GRAJ | Information related to disapproval of communication of intention to grant by the applicant or resumption of examination proceedings by the epo deleted |
Free format text: ORIGINAL CODE: EPIDOSDIGR1 |
|
GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
GRAS | Grant fee paid |
Free format text: ORIGINAL CODE: EPIDOSNIGR3 |
|
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20050601 |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: FG4D Free format text: NOT ENGLISH |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: EP |
|
REF | Corresponds to: |
Ref document number: 60204430 Country of ref document: DE Date of ref document: 20050707 Kind code of ref document: P |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: FG4D Free format text: LANGUAGE OF EP DOCUMENT: FRENCH |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: NV Representative=s name: ISLER & PEDRAZZINI AG |
|
REG | Reference to a national code |
Ref country code: SE Ref legal event code: TRGR |
|
REG | Reference to a national code |
Ref country code: DK Ref legal event code: T3 |
|
GBT | Gb: translation of ep patent filed (gb section 77(6)(a)/1977) |
Effective date: 20050916 |
|
REG | Reference to a national code |
Ref country code: PT Ref legal event code: SC4A Effective date: 20050817 |
|
REG | Reference to a national code |
Ref country code: GR Ref legal event code: EP Ref document number: 20050402724 Country of ref document: GR |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2243694 Country of ref document: ES Kind code of ref document: T3 |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: FD4D |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: MC Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20060228 Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20060228 |
|
PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
26N | No opposition filed |
Effective date: 20060302 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PCAR Free format text: ISLER & PEDRAZZINI AG;POSTFACH 1772;8027 ZUERICH (CH) |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FI Payment date: 20080215 Year of fee payment: 7 Ref country code: SE Payment date: 20080213 Year of fee payment: 7 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: CY Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20050601 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: AT Payment date: 20090227 Year of fee payment: 8 Ref country code: DK Payment date: 20090219 Year of fee payment: 8 Ref country code: ES Payment date: 20090218 Year of fee payment: 8 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: DE Payment date: 20090217 Year of fee payment: 8 Ref country code: NL Payment date: 20090220 Year of fee payment: 8 Ref country code: PT Payment date: 20090219 Year of fee payment: 8 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: CH Payment date: 20090316 Year of fee payment: 8 Ref country code: GB Payment date: 20090217 Year of fee payment: 8 Ref country code: GR Payment date: 20090226 Year of fee payment: 8 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: IT Payment date: 20090217 Year of fee payment: 8 Ref country code: TR Payment date: 20090220 Year of fee payment: 8 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: BE Payment date: 20090408 Year of fee payment: 8 |
|
EUG | Se: european patent has lapsed | ||
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: FI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20090222 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 20090226 Year of fee payment: 8 |
|
BERE | Be: lapsed |
Owner name: *CLL PHARMA Effective date: 20100228 |
|
REG | Reference to a national code |
Ref country code: PT Ref legal event code: MM4A Free format text: LAPSE DUE TO NON-PAYMENT OF FEES Effective date: 20100823 |
|
REG | Reference to a national code |
Ref country code: NL Ref legal event code: V1 Effective date: 20100901 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
REG | Reference to a national code |
Ref country code: DK Ref legal event code: EBP |
|
GBPC | Gb: european patent ceased through non-payment of renewal fee |
Effective date: 20100222 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100228 Ref country code: CH Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100228 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: ST Effective date: 20101029 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: AT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100222 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: DK Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100228 Ref country code: NL Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100901 Ref country code: PT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100823 Ref country code: FR Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100301 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: DE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100901 Ref country code: BE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100228 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100222 Ref country code: GB Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100222 |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FD2A Effective date: 20110405 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20090223 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: ES Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20110323 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: ES Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100223 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: TR Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100222 |